The proposed research will investigate the hypothesis that estrogen has facilitative, and progesterone protective, influences on seizures that can be characterized at physiological levels of these hormones. Female ovariectomized rats implanted with silastic capsules containing estradiol or progesterone to control replacement of these hormones at constant, physiological serum levels will be compared to ovariectomized rats without replacement. Amygdala and frontal cortex kindled seizures will be studied in these rats as comparative models of the generation and spread of seizures. The effects of estradiol on the acquisition and retention of kindled seizures in these models will indicate if estradiol interacts with seizures in limbic and non-limbic areas and with the generalization of seizures between these areas.. Experiments are included to separate a non-specific proconvulsant synergistic effect of estradiol from an interaction with the substrates underlying kindling. Established seizures kindled (amygdala) in the presence of estradiols and to determine if estradiol will be studied for retention of enhanced sensitivity to a proconvulsant effect of estradiol compared to seizures kindled in the absence of estradiol can exert rapid changes in brain excitability or if these changes require time to accumulate. Cross-sensitivity comparisons with pentylenetetrazol will assist in evaluating estradiols proconvulsive potential, and changes in seizure sensitivity in general. Amygdala kindled seizures will be used to study the protective effects of progesterone against established seizure activity and the effects of estradiol and pentylenetetrazol. Physiological ratios of progesterone/estradiol will be included. Comparative studies with phenobarbital will be used to indicate if estradiol has the potential for altering the efficacy of anticonvulsant drugs in general. Limited comparative studies of estradiol and progesterone in male rats will indicate if the female rat brain is especially sensitive to some of the estradiol or progesterone influences on seizure processes. Overall, the proposed research will increase understanding of the interaction of these hormones with seizure generation and spread in particular, and brain excitability in general.